Staghorn calculi are complex renal stones that occupy the majority of the renal collecting system. These stones are associated with high morbidity and can lead to recurrent urinary tract infections, urosepsis, renal deterioration, and death if left untreated. Managing patients with staghorn calculi can be challenging. Fortunately, advances in technology and endourology techniques have enabled urologists to effectively treat these stones with minimal morbidity to the patient. This article describes the contemporary best practices in the initial evaluation, management, and follow up of patients with staghorn calculi to help the practicing urologist navigate this complex condition.